Enhanced G-protein coupled receptors-mediated contraction and reduced endothelium-dependent relaxation in hypertension
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The present study was designed to demonstrate a hypothesis that some G-protein coupled receptors are up-regulated and a dysfunction of endothelium occurs in hypertension. The arteries from hypertensive patients and spontaneously hypertensive rats (SHR) were tested. An in vitro myograph system was used to obtain concentration-contraction curves mediated by endothelin ETA, endothelin ETB, 5-hydroxytryptamine 2A (5HT(2A))-receptors and alpha(1)-adrenoceptors in the arterial segments. In hypertensive patients, the maximum contractions (E-max) induced by endothelin ETB, endothelin ETA and 5-HT receptors were significantly increased with elevated pEC(50) values, while a significantly leftward shift of alpha(1)-adrenoceptor-mediated contraction was seen. Similar results were obtained in SHR. Specific antagonists for 5-HT2A receptors or alpha(1)-adrenoceptors rightward shifted the concentration-contractile curves induced by 5-HT or noradrenalin, while the Emax were not significantly altered, suggesting that the contractions were mediated by 5-HT2A receptors and ocl-adrenoceptors, respectively. Endothelium-dependent maximum relaxation (R-max) in the arterial segments induced by acetylcholine was significantly decreased in both hypertensive patients and SHR. In addition, nitric oxide- and endothelium-derived hyperpolarizing factor-mediated dilatations were decreased significantly and the arterial enclothelial cells were in part lost in SHR. In conclusion, endotheliD ETB, endothelin ETA, 5-HT2A receptor- and alpha-adrenoceptor-mediated contractions were increased in hypertension, while the endotheliurn and its ftinctions were damaged. (c) 2006 Elsevier B.V All rights reserved.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||European Journal of Pharmacology|
|Publication status||Published - 2007|